6. Project Summary The T cell receptor is a multi-subunit receptor complex with four proteins involved in intracellular signal transduction. Almost all studies to date have focused on a signaling motif that is common to all four subunits. We provide preliminary evidence of second signaling motif that is only present in one of the four chains, the CD3 epsilon chain. We term this sequence the basic rich stretch, and have determined that it can interact with a serine/threonine kinase termed GRK2, and can also interact with phospholipids. We will delineate the functional role of this basic rich stretch by modifying it and characterizing the effects of these modifications on 1) T cell receptor and chemokine receptor cross-talk, 2) phospholipid interactions, and 3) T cell development and T cell effector functions. The findings from our studies will yield new mechanistic insights into T cell functions during normal and abnormal immune responses. Novel therapeutic strategies for intervening in T cell functions could emanate from our studies.